ArticleAddiction biology2020
Evaluation of a weighted genetic risk score for the prediction of biomarkers of CYP2A6 activity.
Article in Addiction biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 20 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pharmacogenetics of Nicotine Addiction Treatment (PNAT)
Understanding Disparities in Quitting in African American and White Smokers
Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- The Promise of Polygenic Risk Prediction in Smoking Cessation: Evidence From Two Treatment Trials.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2022Pooled it
- Genome-wide association meta-analysis of nicotine metabolism and cigarette consumption measures in smokers of European descent.Molecular psychiatry · 2021Pooled it
- Relationships Between the Nicotine Metabolite Ratio and Laboratory Assessments of Smoking Reinforcement and Craving Among Adults in a Smoking Cessation Trial.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Trial
- Faster CYP2A6 increases COPD and lung cancer risk by increasing smoking quantity: a mediated mendelian randomization and observational mediation study.Respiratory research · 2026Observational
- Continuous Nicotine Monitors for Personal Nicotine Pharmacokinetics: A Receptor-Aware Research Agenda.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2025Review
- PharmVar GeneFocus: CYP2A6.Clinical pharmacology and therapeutics · 2024Review
- Associating CYP2A6 structural variants with ovarian and lung cancer risk in the UK Biobank: replication and extension.European journal of human genetics : EJHG · 2024Article
- CYP2A6 associates with respiratory disease risk and younger age of diagnosis: a phenome-wide association Mendelian Randomization study.Human molecular genetics · 2024Article
- Genomic medicine to reduce tobacco and related disorders: Translation to precision prevention and treatment.Addiction neuroscience · 2023Article
- Genotyping, characterization, and imputation of known and novel CYP2A6 structural variants using SNP array data.Journal of human genetics · 2023Article
- The use of biomarkers to guide precision treatment for tobacco use.Addiction neuroscience · 2023Article
- Influence of CYP2A6 Genetic Variation, Nicotine Dependence Severity, and Treatment on Smoking Cessation Success.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2023Article
- A scoping review of smoking cessation pharmacogenetic studies to advance future research across racial, ethnic, and ancestral populations.Frontiers in genetics · 2023Article
- Predicting nicotine metabolism across ancestries using genotypes.BMC genomics · 2022Article
- Population pharmacokinetic analysis of dexmedetomidine in children using real-world data from electronic health records and remnant specimens.British journal of clinical pharmacology · 2022Article
- Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes.Clinical and translational science · 2022Article
- Multiethnic Prediction of Nicotine Biomarkers and Association With Nicotine Dependence.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2021Article
- Transferability of Ancestry-Specific and Cross-Ancestry CYP2A6 Activity Genetic Risk Scores in African and European Populations.Clinical pharmacology and therapeutics · 2021Article
- Dissecting the genetic overlap of smoking behaviors, lung cancer, and chronic obstructive pulmonary disease: A focus on nicotinic receptors and nicotine metabolizing enzyme.Genetic epidemiology · 2020Article
- Biochemistry of nicotine metabolism and its relevance to lung cancer.The Journal of biological chemistryReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
The nicotine metabolite ratio (NMR; 3-hydroxycotinine/cotinine) is an index of CYP2A6 activity. CYP2A6 is responsible for nicotine's metabolic inactivation and variation in the NMR/CYP2A6 is associated with several smoking behaviors. Our aim was to integrate established alleles and novel genome-wide association studies (GWAS) signals to create a weighted genetic risk score (wGRS) for the CYP2A6 gene for European-ancestry populations. The wGRS was compared with a previous CYP2A6 gene scoring approach designed for an alternative phenotype (C2/N2; cotinine-d2/(nicotine-d2 + cotinine-d2)). CYP2A6 genotypes and the NMR were assessed in European-ancestry participants. The wGRS training set included N = 933 smokers recruited to the Pharmacogenetics of Nicotine Addiction and Treatment clinical trial [NCT01314001]. The replication cohort included N = 196 smokers recruited to the Quit 2 Live clinical trial [NCT01836276]. Comparisons between the two CYP2A6 phenotypes and with fractional clearance were made in a laboratory-based pharmacokinetic study (N = 92 participants). In both the training and replication sets, the wGRS, which included seven CYP2A6 variants, explained 33.8% (P < 0.001) of the variance in NMR, providing improved predictive power to the NMR phenotype when compared with other CYP2A6 gene scoring approaches. NMR and C2/N2 were strongly correlated to nicotine clearance (ρ = 0.70 and ρ = 0.79, respectively; P < 0.001), and to one another (ρ = 0.82; P < 0.001); however reduced function genotypes occurred in slow NMR but throughout C2/N2. The wGRS was able to predict smoking quantity and nicotine intake, to discriminate between NMR slow and normal metabolizers (AUC = 0.79; P < 0.001), and to replicate previous NMR-stratified cessation outcomes showing unique treatment outcomes between metabolizer groups.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.